Technology drives science and science drives technology. At GNF, both go hand-in-hand as we seek to develop the new tools that allow biological processes to be identified and the underlying mechanisms involved in human disease to be understood. These technologies include genomics and proteomics tools, combinatorial chemistry, cell-based high throughput screening of genes or compounds, structural genomics, and forward/reverse mouse genetics.
Automated technology expertise is an essential tool for scientific discovery. Our Advanced Automation Technologies group identifies, develops, deploys and refines these technologies to accelerate the pace of research breakthroughs throughout the Institute and the larger Novartis organization.
Working closely with other research groups, our team builds and operates automation systems deployed in high throughput flow cytometry, automated cellular profiling, automated tissue culture, protein expression and purification, and ultra-high throughput screening in complex biological assays.
Analytical Chemistry, Metabolism and Pharmacokinetics
The Analytical Chemistry, Metabolism and Pharmacokinetics platform provides logistical support as well as scientific guidance to help project teams more quickly identify and characterize lead candidates. In order to help our scientists focus their attention on science, and not on sample tracking, our compound management group (CMG) employs automation to prepare compounds for testing in various assays. Scientists on the Analytical Chemistry/high-throughput absorption, distribution, metabolism, elimination (HT-ADME) team support open-access analytical instrumentation and conduct chiral separations and in vitro ADME profiling assays. These data are used by project team members (PTMs) from the metabolism and pharmacokinetics (MAP) group to identify lead candidates with optimum ADME properties. MAP scientists also investigate drug metabolism, pharmacokinetics and the relationship of compound exposure and pharmacological effect (PK/PD) of new molecules.
Investigators at GNF employ a wide range of experimental approaches to investigate numerous biological diseases. The Bioinformatics team at GNF works closely with investigators helping to guide experimental plans and optimize the ability for target identification and validation in initiating new drug discovery programs.
The expertise of the group is diverse and includes manipulation and analyses of a wide range of data types such as DNA sequence and expression, global splicing, population genetics in mouse and human to infer causal relationships, in vitro and in vivo functional genetics (shRNA and CRISPR), and others. In addition, the group makes opportunistic use of published data, especially human and mouse genetics and expression data.
Biologics offer a unique opportunity for targeting diseases compared with the mechanism of action typical for small molecule drugs alone. We develop biotherapeutics that combine the selective activity of an antibody coupled with a small molecule for delivery of both cytotoxic and immunomodulatory biotherapeutics. Our portfolio includes antibodies, antibody drug conjugates (ADCs), therapeutic proteins and cell-based therapies.
Leveraging all the fields of protein science – from antibody discovery to protein engineering—is at the core of our approach to biotherapeutics. Our efforts are enhanced by access to custom automation platforms developed in collaboration with GNF’s Engineering group. These platforms enable the production and characterization of a large number of variants to identify and optimize the best biotherapeutic candidate.
Data Science & Data Engineering
The Data Science and Data Engineering group organize and interpret the extensive data generated by drug discovery projects. Our data engineers develop integrated application ecosystems that automate every step of the drug discovery workflow. By applying statistics and the latest machine learning technologies, our team extracts authentic patterns representing the underlying drivers of the biological system.
We utilize a wide range of data science methodologies at GNF. Our success stories include meta- and orthogonal integration of OMICs studies to discover common and unique biological pathways , novel statistical algorithms for prioritizing screening hits , mechanism-of-action characterization of active small molecules through mining profiling databases , and automatic quality control pipelines for large-scale high-throughput screening datasets, among others.
The Engineering team works in close collaboration with research scientists and lab automation specialists to develop equipment and processes that will enable and propel GNF’s strategic scientific initiatives. We are a multi-disciplined team of mechanical, electrical, and software engineers as well as supply chain management and manufacturing specialists. Combining these areas of expertise into one team enable us to bring industrially proven design and manufacturing practices to bear on developing and producing novel, robust laboratory automation and research devices.
Genetic engineering technologies underlie much of the dramatic progress made in understanding biology over the past decades. Tools for genome engineering and strategies for genetic screening have become increasingly refined and efficient.
At GNF we take full advantage of advances in genetics to discover and validate new disease targets. We use both phenotypic screening and site-specific genome editing to address critical issues in disease pathophysiology. In addition to heritable in vivo mutations, we are also interested in somatic cell genetic screening, which can be combined with in vivo readouts such as, for example, immune rejection or muscle regeneration, to monitor biological effects. Robust genetic and genomic assessment is feasible at genome scale using technologies now established at GNF.
The mission of GNF’s Genomics Technologies Group is to identify and validate therapeutic targets for Drug Discovery. To do so, we create, collect, prepare, and employ genome-wide human and mouse gene perturbagens enabling low- and high-throughput functional testing in monoculture cellular models, 3D, organotypic, or co-culture cellular models, and rodents using GNF’s advanced, custom-built automations suites.
We specialize in the use of arrayed-well viral delivery systems, enhancing our ability to profile function in the most therapeutically relevant model systems, and in complex, 3D organotypic screening, shortening the time from target discovery to drug discovery.
We are accelerating the drug discovery process through the convergence of biology, chemistry, and technology using high-throughput screening (HTS). By developing novel assay systems and screening technologies internally, or in collaboration with academic partners, we push the boundaries of the understanding of human disease and the design of new therapies. Our screening platforms provide the foundation to perform these activities quickly, efficiently, and reliably.
Our team develops novel protein or cell based assay systems that capture the biology for a particular disease. We apply GNF-developed, state-of-the-art equipment to quickly assess millions of different chemical structures or biological molecules in order to identify those with the desired properties. The ultimate goal of the effort is to provide fully characterized and modified lead molecules for further investigation as potential therapeutics
The Histology team works closely with research scientists to provide histological expertise to support GNF’s cutting edge science. It is our goal to enhance each project’s success by combining collaboration and communication with state of the art technologies. This includes the use of high throughput immunostaining, in situ hybridization, laser capture confocal microscopy, imaging mass spectrometry and digital pathology. We work closely with internal imaging data scientists to accurately quantify histologic parameters. We are a multi-talented team drawing on expertise from both the research and clinical arenas. The team is committed to making an impact on GNF science and discovery.
Our research focuses on hit finding, lead generation, lead optimization and structure-activity-relationship investigations ultimately leading to viable clinical candidates.
In close collaboration across other GNF teams, we tackle a wide range of target classes such as kinases, proteases, G-protein coupled receptors, and ion channels in various human diseases. Significant efforts are also being made to directly target disease relevant biological pathways using pathway based drug discovery approach. In addition, we collaborate with the protein science group to develop technologies for next generation antibody drug conjugates and beyond.
The Pharmacology team focuses on optimizing and characterizing small molecule and biotherapeutic drug candidates in clinically relevant cellular and animal models. We design, execute and interpret pharmacology studies critical for progressing internal drug discovery projects and in partnership with external collaborators. Our scientists provide technical expertise and support to help project teams understand how the pharmacodynamics of drug candidates influences the physiology in relevant biological systems.
The group also plays an important supporting role in validating novel drug targets in disease models and in preclinical drug candidate selection.
The Protein Science group uses macromolecular structural information to facilitate the design of novel protein and small molecule therapeutics. Our scientists study cells, cellular processes and disease at the protein level, probing the interactions between targeted macromolecules and therapeutic candidates at atomic resolution to improve the characteristics of lead molecules.
We use a comprehensive suite of biophysical and bioanalytical tools for tasks ranging from the elucidation of fundamental biology to the optimization of a biotherapeutic lead candidate. We are also focused on a better understanding of signaling cascades that control a wide range if biological processes and potential targets for new medicines